Kit signaling pathway module

Stem cell factor (KIT ligand) binds and dimerizes the class III receptor tyrosine kinase KIT, whose autophosphorylated intracellular tyrosines recruit SH2-domain effectors (GRB2, PI3K p85, SHP2, Src-family kinases) that drive Ras-MAPK, PI3K-AKT, and STAT5 outputs controlling survival, proliferation, and migration of hematopoietic progenitors, mast cells, melanocytes, germ cells, and interstitial cells of Cajal.

Curated compact signaling-pathway module built to the same three-step template as the sibling receptor tyrosine kinase modules (pdgfr_signaling, egfr_signaling, fgfr_signaling): ligand engagement, phosphotyrosine effector recruitment, and downstream output. KIT is a class III receptor tyrosine kinase in the same PANTHER family (PTHR24416) as PDGFRA/PDGFRB, CSF1R, and FLT3; the module is kept separate from pdgfr_signaling because GO models Kit signaling as its own pathway term (GO:0038109) with its own PAINT node (PTN002814378) and its own ligand (KITLG, family PTHR11574, which has no PAINT IBD seed row for P21583, so no PTN anchor is assertable and KITLG is grounded as a verified UniProt exemplar). Effector choice follows the reviews cited in evidence: GRB2 and PI3K p85 are the canonical SH2 adaptors recruited to phosphorylated KIT, SHP2 (PTPN11) is the KIT-associated phosphatase that couples to the Ras-ERK branch, and LYN is the Src-family kinase representative for the juxtamembrane phosphotyrosine docking site. Downstream outputs are limited to the three branches with GOA support on human KIT: positive regulation of MAPK cascade (IMP) and STAT activation (IMP, PMID:21135090) are experimentally grounded, while the PI3K-AKT branch (GO:0051897) is supported only by TAS (PMID:16129412); PLCG1 and other Ras-branch components are deliberately left to broader modules. PTN anchors are included only when the exemplar accession appears in an IBD seed row in interpro/panther; roles without local PAINT seeds remain grounded by verified UniProt exemplar accessions. UniProt protein names were taken verbatim from the UniProt REST API; PANTHER family labels from interpro/panther/panther.obo; PMIDs and titles were checked against PubMed. All nine human members (KIT, KITLG, GRB2, PIK3R1, PTPN11, LYN, SOS1, PIK3CA, STAT5A) now have curated gene reviews in genes/human, and gocams/index.tsv contains no KIT activity, so this module is not yet cross-checked against a production GO-CAM. Taxonomic scope: the class III RTK family (PTHR24416) is metazoan-deep, but the discrete Kit signaling pathway (GO:0038109) and the KIT-KITLG ligand-receptor pair are a bony-vertebrate feature (the IBD node carrying GO:0038109/GO:0046427, PTN002814378, is placed at NCBITaxon:117571 Euteleostomi); downstream effectors are ancient and shared across RTK pathways. As an alternate-species exemplar documenting teleost variation, the zebrafish co-orthologs kita (Q8JFR5, the sparse mutant) and kitlga (Q56JH6) were reviewed (genes/DANRE/kita, genes/DANRE/kitlga): they arose from the teleost whole-genome duplication and retain the ancestral pigmentation/hematopoiesis roles, while the paralogs kitb and kitlgb diverged and do not fully compensate, so zebrafish is not a one-to-one substitute for mammalian KIT/KITLG. Falcon integration (2026-09-25): Falcon findings are linked as evidence; the report's characterization of STAT5 as a conditional, lineage-dependent output is reflected in the output-step description and in the recorded knowledge gap. Automatically extracted open-question headings were not retained as knowledge_gap entries because they were not manually curated, and machine-generated Falcon citations remain curation support rather than adjudicated references.